Identification of Early Warning Signals of Infectious Diseases in Hospitals by Integrating Clinical Treatment and Disease Prevention.

The global incidence of infectious diseases has increased in recent years, posing a significant threat to human health. Hospitals typically serve as frontline institutions for detecting infectious diseases. However, accurately identifying warning signals of infectious diseases in a timely manner, especially emerging infectious diseases, can be challenging. Consequently, there is a pressing need to integrate treatment and disease prevention data to conduct comprehensive analyses aimed at preventing and controlling infectious diseases within hospitals. This paper examines the role of medical data in the early identification of infectious diseases, explores early warning technologies for infectious disease recognition, and assesses monitoring and early warning mechanisms for infectious diseases. We propose that hospitals adopt novel multidimensional early warning technologies to mine and analyze medical data from various systems, in compliance with national strategies to integrate clinical treatment and disease prevention. Furthermore, hospitals should establish institution-specific, clinical-based early warning models for infectious diseases to actively monitor early signals and enhance preparedness for infectious disease prevention and control.

Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Antibiotic heteroresistance in Klebsiella pneumoniae: Definition, detection methods, mechanisms, and combination therapy.

Klebsiella pneumoniae is a common opportunistic pathogen that presents significant challenges in the treatment of infections due to its resistance to multiple antibiotics. In recent years, K. pneumoniae has been reported for the development of heteroresistance, a phenomenon where subpopulations of the susceptible bacteria exhibit resistance. This heteroresistance has been associated with increased morbidity and mortality rates. Complicating matters further, its definition and detection pose challenges, often leading to its oversight or misdiagnosis. Various mechanisms contribute to the development of heteroresistance in K. pneumoniae, and these mechanisms differ among different antibiotics. Even for the same antibiotic, multiple mechanisms may be involved. However, our current understanding of these mechanisms remains incomplete, and further research is needed to gain a more comprehensive understanding of heteroresistance. While the clinical recommendation is to use combination antibiotic therapy to mitigate heteroresistance, this approach also comes with several drawbacks and potential adverse effects. In this review, we discuss the definition, detection methods, molecular mechanisms, and treatment of heterogenic resistance, aiming to pave the way for more effective treatment and management in the future. However, addressing the problem of heteroresistance in K. pneumoniae represents a long and complex journey that necessitates comprehensive research efforts.

NK-92MI Cells Engineered with Anti-claudin-6 Chimeric Antigen Receptors in Immunotherapy for Ovarian Cancer.

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.

The novel HLA-B*58:144N allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*58:144N differs from HLA-B*58:01:01:01 by one nucleotide in exon 2.

Porphyromonas gingivalis promotes the progression of oral squamous cell carcinoma by stimulating the release of neutrophil extracellular traps in the tumor immune microenvironment.

BACKGROUND: The aim of this study was to investigate the impact of Porphyromonas gingivalis (P. gingivalis) on the progression of oral squamous cell carcinoma (OSCC) through neutrophil extracellular traps (NETs) in the tumor immune microenvironment. METHODS: The expression of NETs-related markers was identified through immunohistochemistry, immunofluorescence, and Western blotting in different clinical stages of OSCC samples. The relationship between NETs-related markers and clinicopathological characteristics in 180 samples was analyzed using immunohistochemistry data. Furthermore, the ability to predict the prognosis of OSCC patients was determined by ROC curve analysis and survival analysis. The effect of P. gingivalis on the release of NETs was identified through immunofluorescence and immunohistochemistry, both in vitro and in vivo. CAL27 and SCC25 cell lines were subjected to NETs stimulation to elucidate the influence of NETs on various cellular processes, including cell proliferation, migration, invasion, and metastasis in vitro. Furthermore, the impact of NETs on the growth and metastatic potential of OSCC was assessed using in vivo models involving tumor-bearing mice and tumor metastasis mouse models. RESULTS: Immunochemistry analysis revealed a significant correlation between the NETs-related markers and clinical stage, living status as well as TN stage. P. gingivalis has demonstrated its ability to effectively induce the release of NETs both in vivo and in vitro. NETs have the potential to facilitate cell migration, invasion, and colony formation. Moreover, in vivo experiments have demonstrated that NETs play a pivotal role in promoting tumor metastasis. CONCLUSION: High expression of NETs-related markers demonstrates a strong correlation with the progression of OSCC. Inhibition of the NETs release process stimulated by P. gingivalis and targeted NETs could potentially open up a novel avenue in the field of immunotherapy for patients afflicted with OSCC.

Investigation of anti-diabetic effect of a novel coenzyme Q10 derivative.

Introduction: The rising incidence of type 2 diabetes has seriously affected international public health. The search for more drugs that can effectively treat diabetes has become a cutting-edge trend in research. Coenzyme Q10 (CoQ10) has attracted much attention in the last decade due to its wide range of biological activities. Many researchers have explored the clinical effects of CoQ10 in patients with type 2 diabetes. However, CoQ10 has low bio-availability due to its high lipophilicity. Therefore, we have structurally optimized CoQ10 in an attempt to exploit the potential of its pharmacological activity. Methods: A novel coenzyme Q10 derivative (L-50) was designed and synthesized by introducing a group containing bromine atom and hydroxyl at the terminal of coenzyme Q10 (CoQ10), and the antidiabetic effect of L-50 was investigated by cellular assays and animal experiments. Results: Cytotoxicity results showed that L-50 was comparatively low toxicity to HepG2 cells. Hypoglycemic assays indicated that L-50 could increase glucose uptake in IR-HepG2 cells, with significantly enhanced hypoglycemic capacity compared to the CoQ10. In addition, L-50 improved cellular utilization of glucose through reduction of reactive oxygen species (ROS) accumulated in insulin-resistant HepG2 cells (IR-HepG2) and regulation of JNK/AKT/GSK3ß signaling pathway, resulting in hypoglycemic effects. Furthermore, the animal experiments demonstrated that L-50 could restore the body weight of HFD/STZ mice. Notably, the findings suggested that L-50 could improve glycemic and lipid metabolism in HFD/STZ mice. Moreover, L-50 could increase fasting insulin levels (FINS) in HFD/STZ mice, leading to a decrease in fasting blood glucose (FBG) and hepatic glycogen. Furthermore, L-50 could recover triglycerides (TG), total cholesterol (T-CHO), lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) levels in HFD/STZ mice. Discussion: The addition of a bromine atom and a hydroxyl group to CoQ10 could enhance its anti-diabetic activity. It is anticipated that L-50 could be a promising new agent for T2DM.

[Quality evaluation of Lysimachiae Herba from different habitats based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis].

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 µm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.

Tetrachlorovancomycin: Total Synthesis of a Designed Glycopeptide Antibiotic of Reduced Synthetic Complexity.

A technically straightforward total synthesis of a new class of vancomycin analogues of reduced synthetic complexity was developed that provided tetrachlorovancomycin (1, LLS = 15 steps, 15% overall yield) and its precursor aglycon 29 (nearly 20% overall yield). The class retains all the intricate vancomycin structural features that contribute to its target binding affinity and selectivity, maintains the antimicrobial activity of vancomycin, and achieves the simplification by an unusual addition, not removal, of benign substituents to the core structure. The modification, accomplished by addition of two aryl chloride substituents to provide 1, permitted a streamlined total synthesis of the new glycopeptide antibiotic class by removing the challenges associated with CD and DE ring system atropisomer stereochemical control. This also enabled their simultaneous and further-activated SNAr macrocyclizations that establish the tricyclic skeleton of 1. Key elements of the approach include catalyst-controlled diastereoselective formation of the AB biaryl axis of chirality (>30:1 dr), an essentially instantaneous macrolactamization of the AB ring system free of competitive epimerization (>30:1 dr), racemization free coupling of the E ring tetrapeptide, room temperature simultaneous CD and DE ring system cyclizations, a highly refined 4-step conversion of the cyclization product to the aglycon, and a protecting-group-free one-pot enzymatic glycosylation for disaccharide introduction. In addition to the antimicrobial evaluation of tetrachlorovancomycin (1), the preparation of key peripherally modified derivatives, which introduce independent and synergistic mechanisms of action, revealed their exceptional antimicrobial potency and provide the foundation for future use of this new class of synthetic glycopeptide analogues.

Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment.

The pathogenesis of intervertebral disc degeneration (IVDD) is attributed to metabolic dysregulation within the extracellular matrix and heightened apoptosis of nucleus pulposus cells (NPC). Therefore, a potential therapeutic strategy for managing IVDD involves the reestablishment of metabolic equilibrium within the extracellular matrix and the suppression of excessive myeloid cell apoptosis. The microRNA, miR-5590, displays marked differential expression in degenerative nucleus pulposus (NP) tissues and exerts a direct influence on the regulation of DDX5 expression. This, in turn, modulates mammalian target of rapamycin (mTOR) phosphorylation, thereby impacting autophagy and apoptosis. However, ensuring the smooth delivery of miRNA to a specific injury site poses a significant challenge. To address this issue, a multifunctional DNA hydrogel was developed and subsequently loaded with miR-5590 via spherical nucleic acids (SNAs) for the treatment of IVDD. The hydrogel, which exhibits versatility, has the potential to be administered through injection at the site of injury, resulting in a consistent and prolonged release of miR-5590. This leads to the creation of a genetic microenvironment within the NP, which triggers the onset of autophagy in NPCs and subsequently suppresses apoptosis. As a result, this process regulates the metabolic equilibrium within the extracellular matrix, thereby impeding the in vitro and in vivo progression of IVDD. The amalgamation of miRNAs and biomaterials offers a promising therapeutic strategy for the management of IVDD in clinical settings.

Small Extracellular Vesicles Secreted by Peri-urethral Tissues Regulate Fibroblast Function and Contribute to the Pathogenesis of Female Stress Urinary Incontinence.

OBJECTIVE: This study aimed to explore the existence of small extracellular vesicles (sEVs) in peri-urethral tissues and the role of abnormal expression of sEVs in the pathogenesis of female stress urinary incontinence (SUI). METHODS: sEVs were extracted from peri-urethral vaginal wall tissues using differential centrifugation and were observed by transmission electron microscopy (TEM). The number of sEVs and their protein contents were compared between SUI and control groups using nanoparticle tracking analysis (NTA) and bicinchoninic acid (BCA) protein assay. Fibroblasts were cultured separately with SUI (SsEVs group) and normal tissue sEVs (NsEVs group). Proliferation and migration of fibroblasts were compared between groups using CCK-8 and wound healing assays, respectively. Expression levels of collagen I and III were compared among blank control (BC), NsEVs, and SsEVs groups using real-time PCR. Protein mass spectrometry was used to test the differentially expressed proteins contained in sEVs between groups. RESULTS: sEVs were extracted and found under the electron microscope. There were significantly more sEVs extracted from the SUI group compared to the normal group. Fibroblasts showed increased proliferative and decreased migratory abilities, and expressed more collagen in the SsEVs group compared to the NsEVs and BC groups. Protein spectrum analysis demonstrated several differentially expressed targets, including components of microfibrils, elastin polymer, and anti-inflammatory factors. CONCLUSION: sEVs were detected in the peri-urethral tissues. SUI tissues expressed more sEVs than control. The abnormal expression of sEVs and their protein contents may contribute to the pathogenesis and progression of SUI.

[Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum].

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 µm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.

PLAU and LAMC2 can predict a poor prognosis in patients with HNSCC.

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck. However, the molecular mechanisms governing the development of HNSCC have not been fully elucidated. Materials and Methods: Differentially expressed genes (DEGs) were screened out from The Cancer Genome Atlas (TCGA) and GSE23036 datasets. Weighted gene coexpression network analysis (WGCNA) was used to reveal the correlations among genes and to search for significantly correlated gene modules. The expression levels of genes in HNSCC and normal samples according to antibody-based detected methods was assessed by utilizing the Human Protein Atlas (HPA). The impact of the selected hub genes on the prognosis of HNSCC patients was assessed by analysing immunohistochemistry (IHC) and immunofluorescence (IF) expression levels and clinical data. Results: Twenty-four genes positively correlated with tumour status and 15 genes negatively correlated with tumour status were screened out by WGCNA. PLAU and LAMC2 were associated with a poor prognosis in patients with HNSCC and were finally screened out and verified by GEPIA and HPA database analysis. Immunohistochemistry of samples collected from 175 patients with HNSCC and subsequent statistical analysis also showed that PLAU and LAMC2 were associated with a poor prognosis in patients with HNSCC, and the levels of these two factors were positively correlated. The expression and co-localization of PLAU and LAMC2 in HNSCC tissues were confirmed by double immunofluorescence labeling. Conclusions: There was a positive correlation between PLAU and LAMC2 expression in HNSCC samples, and PLAU and LAMC2 might be independent prognostic biomarkers for HNSCC.

Divergent Total Synthesis and Characterization of Maxamycins.

A new streamlined and scaled divergent total synthesis of pocket-modified vancomycin analogs is detailed that provides a common late-stage intermediate [Ψ[C(═S)NH]Tpg4]vancomycin (LLS = 18 steps, 12% overall yield, >5 g prepared) to access both existing and future pocket modifications. Highlights of the approach include an atroposelective synthesis of [Ψ[C(═S)NH]Tpg4]vancomycin aglycon (11), a one-pot enzymatic glycosylation for direct conversion to [Ψ[C(═S)NH]Tpg4]vancomycin (12), and new powerful methods for the late-stage conversion of the embedded thioamide to amidine/aminomethylene pocket modifications. Incorporation of two peripheral modifications provides a scalable total synthesis of the maxamycins, all prepared from aglycon 11 without use of protecting groups. Thus, both existing and presently unexplored pocket-modified analogues paired with a range of peripheral modifications are accessible from this common thioamide intermediate. In addition to providing an improved synthesis of the initial member of the maxamycins, this is illustrated herein with the first synthesis and examination of maxamycins that contain the most effective of the pocket modifications (amidine) described to date combined with two additional peripheral modifications. These new amidine-based maxamycins proved to be potent, durable, and efficacious antimicrobial agents that display equipotent activity against vancomycin-sensitive and vancomycin-resistant Gram-positive organisms and act by three independent synergistic mechanisms of action. In the first such study conducted to date, one new maxamycin (21, MX-4) exhibited efficacious in vivo activity against a feared and especially challenging multidrug-resistant (MRSA) and vancomycin-resistant (VRSA) S. aureus bacterial strain (VanA VRS-2) for which vancomycin is inactive.

Inflammatory response-related genes predict prognosis in patients with HNSCC.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck, and the inflammatory microenvironment can impact the prognosis of HNSCC. However, the contribution of inflammation to tumour progression has not been fully elucidated. METHODS: The mRNA expression profiles and corresponding clinical data of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The least absolute shrinkage and selection operator (LASSO) Cox analysis model was used to identify prognostic genes. The overall survival (OS) between high- and low-risk patients was compared by Kaplan‒Meier analysis. The independent predictors of OS were determined by univariate and multivariate Cox analyses. Single-sample gene set enrichment analysis (ssGSEA) was used to assess immune cell infiltration and immune-related pathway activity. GSEA was used to analyse Gene Ontology (GO) terms and Kyoto encyclopaedia of Genes and Genomes (KEGG) pathways. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to examine prognostic genes in HNSCC patients. Immunohistochemistry was used to verify the protein expression of prognostic genes in HNSCC samples. RESULTS: An inflammatory response-related gene signature was constructed by LASSO Cox regression analysis. HNSCC patients in the high-risk group showed significantly reduced OS compared with those in the low-risk group. The predictive capacity of the prognostic gene signature was confirmed by ROC curve analysis. Multivariate Cox analysis revealed that the risk score was an independent predictor for OS. Functional analysis indicated that the immune status was markedly different between the two risk groups. The risk score was significantly related to tumour stage and immune subtype. The expression levels of the prognostic genes were significantly related to the sensitivity of cancer cells to antitumour drugs. Furthermore, high expression of the prognostic genes significantly predicted poor prognosis of HNSCC patients. CONCLUSIONS: The novel signature containing 9 inflammatory response-related genes reflects the immune status of HNSCC and can be used for prognosis prediction. Furthermore, the genes may be potential targets for HNSCC treatment.

Risk factors for misdiagnosis in children with developmental dysplasia of the hip: a retrospective single centre study.

OBJECTIVE: To investigate risk factors of misdiagnosis at the first visit of children with developmental dysplasia of the hip (DDH) who did not participate in hip ultrasound screening. METHODS: A retrospective review was conducted on children with DDH admitted to a tertiary hospital in northwestern China between January 2010 and June 2021. We divided the patients into the diagnosis and misdiagnosis groups according to whether they were diagnosed at the first visit. The basic information, treatment process and medical information of the children were investigated. We made a line chart of the annual misdiagnosis rate to observe the trend in the annual misdiagnosis rate. Univariate and multivariate logistic regression analyses were used to identify significant risk factors for missed diagnosis. RESULTS: A total of 351 patients met the inclusion criteria, including 256 (72.9%) patients in the diagnosis group and 95 (27.1%) patients in the misdiagnosis group. The line chart of the annual rate of misdiagnoses among children with DDH from 2010 to 2020 showed no significant change trend. Multiple logistic regression analysis showed that the paediatrics department (v the paediatric orthopaedics department: OR 0.21, p<0.001), the general orthopaedics department (v the paediatric orthopaedics department: OR 0.39, p=0.006) and the senior physician (v the junior physician: OR 2.47, p=0.006) on the misdiagnosis at the first visit of children were statistically significant. CONCLUSION: Children with DDH without hip ultrasound screening are prone to be misdiagnosed at their first visit. The annual misdiagnosis rate has not been significantly reduced in recent years. The department and title of the physician are independent risk factors for misdiagnosis.

A comprehensive study on flocculation of anionic dyes using the bioflocculant produced by Bacillus thuringiensis: Kinetics, affecting factors, and perspectives.

Bioflocculants have received more and more attention as alternatives to chemical flocculants because of their innocuousness, environmental friendliness, and high effectiveness. This study aims to investigate various factors that influence the performance of the novel bioflocculant produced by Bacillus thuringiensis (BF-TWB10) and analyze its adsorption kinetics to optimize its flocculation performance for real applications. The best-fit kinetic model was pseudo-second order with R2 = 0.999. The effects of pretreatment temperature, pH, and the presence of cations on flocculation were assessed. Further investigations of flocculation, including zeta potential analysis and particle size analysis, were also conducted. Thermal pretreatment of BF-TWB10 or the presence of divalent cations could stimulate the decolorization efficiency of the bioflocculant. BF-TWB10 manifested outstanding dye removal performances with over 90% for all tested anionic dyes at pH 2 and 3. Its decolorization efficiency on anionic dyes decreased with the increase of pH values. Zeta potential analysis revealed that the electrostatic repulsion between anionic dyes decreased after the addition of BT-TWB10 and further diminished by adjusting the reaction mixture to pH 2 before flocculation, suggesting the occurrence of adsorption bridging and charge neutralization. These findings proposed that BF-TWB10 might be a promising bioflocculant for the removal of dyes in textile wastewater. PRACTITIONER POINTS: Bioflocculant BF-TWB10 shows outstanding performance in flocculation. Adsorption process follows pseudo-second-order kinetic model. Flocculation process is pH-responsive. High-temperature pretreatment or divalent cations enhance its flocculation performance. The analyses suggest the occurrence of charge neutralization and adsorption bridging.

Advances in the application of induced pluripotent stem cells in pediatric diseases.

The optimal diagnosis and treatment of pediatric diseases depend on more adequate understanding of pathophysiology. The advent of induced pluripotent stem cells (iPSCs) has provided new strategies for the research and therapy of pediatric diseases. iPSCs are pluripotent stem cells induced by reprogramming of mature cells. Now they can be induced from many types of somatic cells (such as fibroblasts, peripheral blood mononuclear cells and urine cells).With the improvement of various reprogramming methods, its generation procedure is more and more optimized, and the use of small molecules to induce iPSCs is one of the research focus now. Due to their ability to differentiate into a variety of cells, combined with the development of gene editing technology, iPSCs have been increasingly favored in the modeling of diseases and cell therapy, especially hereditary diseases, and have achieved some success in clinical treatment. But before they can be widely used in clinical treatment, there are still some problems to be solved, such as tumorigenicity, immunogenicity and heterogeneity. This article reviewed the source of iPSCs, reprogramming technology, applications of iPSCs in common childhood diseases, current problems and prospects, in order to deepen the understanding of iPSCs and provide reference for in-depth research in field of exploring mechanisms of diseases and therapy of diseases.

Identification of DELLA gene family in head cabbage and analysis of mRNA transport in the heterograft.

DELLA gene family is involved in the regulation of signal transduction of plant hormones. mRNAs of GA insensitive (GAI), the member of DELLA gene family, are also signaling molecules of long-distance transport in plants. Genome-wide identification and mRNA transport analysis of the members of DELLA gene family in head cabbage (Brassica oleracea var. capitata) can provide basic data for their application in head cabbage. In this study, five members of DELLA gene family (BoRGA1, BoRGA2, BoRGL1, BoRGL2, and BoRGL3) were identified in head cabbage using genome and transcriptome data. However, head cabbage lacked a GAI gene in its genome. The scion (head cabbage, inbred line G27) and the rootstock Chinese flowering cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee) (sijiucaixin) were cleft-grafted together to produce the heterograft. Inflorescence stem of the rootstock and the corresponding inflorescence stem in Chinese flowering cabbage seedlings (as controls) were purified and analyzed with transcriptome sequencing. The total of 8, 9, 3, 5, and 1 exogenous read(s), derived respectively from BoRGA1, BoRGA2, BoRGL1, BoRGL2, and BoRGL3, were identified in the transcriptomes of the rootstocks. Nevertheless, mRNA transport of DELLA family genes from scion to rootstock did not increase the transcriptional level of the members of DELLA gene family in the rootstocks. Correlation analysis suggested that mRNA transport efficiency of the DELLA family genes was correlated with the sequence and the transcriptional level of the respective DELLA gene in the scion (head cabbage). This study lays the foundation for further investigation on the molecular mechanism of mRNA transport of the members of DELLA gene family in head cabbage.